Autoimmune T cell responses to antigenic peptides presented by bronchoalveolar lavage cell HLA-DR molecules in sarcoidosis

Clin Immunol. 2009 Dec;133(3):353-63. doi: 10.1016/j.clim.2009.08.008. Epub 2009 Sep 27.

Abstract

The etiology of sarcoidosis remains unknown. Recently, by mass spectrometric sequencing of peptides eluted from HLA-DR molecules of bronchoalveolar lavage (BAL) cells from DRB10301(pos) patients, we identified potential self-antigens in sarcoidosis. The aim of the present study was to investigate the capacity of selected peptides to stimulate lung and blood T cells of sarcoidosis patients using an interferon-gamma ELISPOT assay. In peripheral blood, there were strong T cell responses to a peptide derived from the cytoskeletal protein vimentin in 6 out of 11 DRB10301(pos) patients with active disease but not in patients with other HLA types. BAL T cell responses against peptides derived from ATP synthase or from lysyl-tRNA synthetase were detected in DRB10301(pos) as well as DRB10301(neg) patients. By using antigenic peptides presented in vivo in the lungs of sarcoidosis patients, we have identified blood and lung T cell autoimmune responses that may help sustain the inflammation in this disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acid Sequence
  • Amino Acyl-tRNA Synthetases / immunology
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology*
  • Bronchoscopy
  • CD4-Positive T-Lymphocytes / immunology*
  • DNA / chemistry
  • DNA / genetics
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genotype
  • HLA-DR Antigens / genetics
  • HLA-DR Antigens / immunology*
  • HLA-DRB1 Chains
  • Humans
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Molecular Sequence Data
  • Peptide Fragments / immunology*
  • Polymerase Chain Reaction
  • Sarcoidosis, Pulmonary / blood
  • Sarcoidosis, Pulmonary / immunology*
  • Statistics, Nonparametric
  • Vimentin / immunology

Substances

  • Autoantibodies
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Peptide Fragments
  • Vimentin
  • DNA
  • Amino Acyl-tRNA Synthetases